Abstract

Background

Physiologic changes quantified by diffusion and perfusion MRI have shown utility in predicting treatment response in glioblastoma (GBM) patients treated with cytotoxic therapies. We aimed to investigate whether quantitative changes in diffusion and perfusion after treatment by immune checkpoint inhibitors (ICIs) would determine 6-month progression-free survival (PFS6) in patients with recurrent GBM.

Methods

Inclusion criteria for this retrospective study were: (i) diagnosis of recurrent GBM treated with ICIs and (ii) availability of diffusion and perfusion in pre and post ICI MRI (iii) at ≥6 months follow-up from treatment. After co-registration, mean values of the relative apparent diffusion coefficient (rADC), K^trans (volume transfer constant), Ve (extravascular extracellular space volume) and Vp (plasma volume), and relative cerebral blood volume (rCBV) were calculated from a volume-of-interest of the enhancing tumor. Final assignment of stable/improved versus progressive disease was determined on 6-month follow-up using modified Response Assessment in Neuro-Oncology criteria.

Results

Out of 19 patients who met inclusion criteria and follow-up (mean ± SD: 7.8 ± 1.4 mo), 12 were determined to have tumor progression, while 7 had treatment response after 6 months of ICI treatment. Only interval change of rADC was suggestive of treatment response. Patients with treatment response (6/7: 86%) had interval increased rADC, while 11/12 (92%) with tumor progression had decreased rADC (P = 0.001). Interval change in rCBV, K^trans, Vp, and Ve were not indicative of treatment response within 6 months.

Conclusions

In patients with recurrent GBM, interval change in rADC is promising in assessing treatment response versus progression within the first 6 months following ICI treatment.

Key Points

• In recurrent GBM treated with ICIs, interval change in rADC suggests early treatment response.• Interval change in rADC can be used as an imaging biomarker to determine PFS6.• Interval change in MR perfusion and permeability measures do not suggest ICI treatment response.

中文翻译：

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多参数MRI可早期识别免疫检查点抑制剂治疗的复发性胶质母细胞瘤的治疗反应

摘要

背景

通过扩散和灌注MRI量化的生理变化已显示出可用于预测接受细胞毒疗法治疗的胶质母细胞瘤（GBM）患者的治疗反应。我们旨在调查免疫检查点抑制剂（ICI）治疗后扩散和灌注的定量变化是否将确定复发性GBM患者的6个月无进展生存期（PFS6）。

方法

这项回顾性研究的纳入标准为：（i）用ICI治疗的复发性GBM的诊断，以及（ii）ICI MRI之前和之后MRI扩散和灌注的可用性（iii）治疗后≥6个月的随访。共注册后，根据以下公式计算相对表观扩散系数（rADC），K ^trans（体积转移常数），Ve（血管外细胞外空间体积）和Vp（血浆体积）和相对脑血体积（rCBV）的平均值感兴趣的肿瘤体积。在6个月的随访中，使用改良后的神经肿瘤反应评估标准确定了稳定/改善与进行性疾病的最终分配。

结果

在19名符合入组标准和随访（平均±SD：7.8±1.4个月）的患者中，有12名被确定患有肿瘤进展，而7名在ICI治疗6个月后有治疗反应。仅rADC的间隔改变提示治疗反应。有治疗反应的患者（6/7：86％）的间隔rADC升高，而有肿瘤进展的11/12（92％）的rADC降低（P = 0.001）。rCBV，K ^trans，Vp和Ve的间隔变化并不表示6个月内的治疗反应。

结论

对于复发性GBM患者，rADC的间隔变化有望评估ICI治疗后前6个月内的治疗反应与进展。

关键点

•在接受ICI治疗的复发性GBM中，rADC的间隔改变提示早期治疗反应。•rADC的间隔改变可用作影像学生物标志物以确定PFS6。•MR灌注和通透性测量的间隔改变并不提示ICI治疗反应。